Italy’s top criminal court dealt a stunning setback Tuesday to the 25-year-old college student, overturning her acquittal in the grisly murder of her British roommate and ordering her to stand trial again.

“She thought that the nightmare was over,” Knox’s attorney, Carlo Dalla Vedova, told reporters minutes after conveying the unexpected turn of events to his client, who had stayed up to hear the ruling, which came shortly after 2 a.m. West Coast time. “But she’s ready to fight.”

Now a student at the University of Washington in Seattle, Knox called the decision by the Rome-based Court of Cassation “painful” but said she was confident that she would be exonerated.

The American left Italy a free woman after her October 2011 acquittal — but only after serving nearly four years of a 26-year prison sentence from a lower court that convicted her of murdering Meredith Kercher. The 21-year-old exchange student’s body was found in a pool of blood, her throat slit, in a bedroom of the house the two shared in Perugia, a university town 100 miles north of Rome.

Raffaele Sollecito, Knox’s Italian boyfriend at the time, was also convicted of the Nov. 1, 2007, murder, then later acquitted. His acquittal was also thrown out Tuesday and a new trial ordered.

Italian law cannot compel Knox to return for the new trial and Dalla Vedova said she had no plans to do so.

In any case, the judicial saga is likely to continue for years. It will be months before a date is set for the new trial, to be held in Florence instead of Perugia because the small town has only one appellate court, which already acquitted her.

Prosecution and defense teams must also await details of the ruling explaining why the high court concluded there were procedural errors in the trial that acquitted Knox and Sollecito. The court has 90 days to issue its explanation.

Another Knox defender, Luciano Ghirga, said she was gearing up psychologically for her third trial. Ghirga said he told Knox: “You have always been our strength. We rose up again after the first-level convictions. We’ll have the same resoluteness, the same energy” in the new trial.

Still, it was a tough blow for the former exchange student, whose parents mortgaged both their homes to raise funds for her lengthy, expensive defense.

“It was painful to receive the news that the Italian Supreme Court decided to send my case back for revision when the prosecution’s theory of my involvement in Meredith’s murder has been repeatedly revealed to be completely unfounded and unfair,” Knox said in a statement.

She said the matter must now be examined by “an objective investigation and a capable prosecution.”

“No matter what happens, my family and I will face this continuing legal battle as we always have, confident in the truth and with our heads held high in the face of wrongful accusations and unreasonable adversity,” Knox said.

Prosecutors alleged that Kercher was the victim of a drug-fueled sex game gone awry. Knox, then 20, and Sollecito, then 24, denied wrongdoing and said they weren’t even in the apartment that night, although they acknowledged they had smoked marijuana and their memories were clouded.

An Ivory Coast man, Rudy Guede, was convicted of the slaying in a separate trial and is serving a 16-year sentence.

Sollecito, whose 29th birthday was Tuesday, sounded shaken when a reporter reached him by phone.

“Now I can’t say anything,” said the Italian, who has been studying computer science in the northern city of Verona after finishing up an earlier degree while in prison.

A local Italian news report quoted Sollecito’s current girlfriend as saying he and Knox spoke by phone and described him as being psychologically destroyed.

His lawyer, Luca Maori, said neither Sollecito nor Knox ran any danger of being arrested. “It’s not as if the lower-court convictions are revived,” he said, noting that the high court didn’t determine “whether the two were innocent or guilty. “

For those familiar with the U.S. legal principle of “double jeopardy” — which holds that no one acquitted of a crime can be tried again for it — the idea that the Italian justice system allows prosecutors to appeal acquittals is hard to absorb.

Knox attorney Dalla Vedova dismissed the “double jeopardy” concern, maintaining the high court ruling hadn’t decided the defendants’ guilt or innocence, but merely ordered a fresh appeals trial, which he said was unlikely to start before early 2014.

The appeals court that acquitted Knox and Sollecito had criticized virtually the entire prosecution case, especially the forensic evidence that helped clinch their 2009 convictions. It noted the murder weapon was never found, and said DNA tests were faulty and that prosecutors provided no murder motive.

In arguing for overturning the acquittals, prosecutors said the Perugia appellate court was too dismissive of DNA tests on a knife they maintained could have been used to slash Kercher’s throat as well as DNA traces on a bra belonging to the victim and tests done on blood stains in the bedroom and bathroom.

The court on Tuesday also upheld a slander conviction against Knox. During a 14-hour police interrogation, she had accused a local Perugia pub owner of carrying out the killing. The man was held for two weeks, based on her allegations, before being released for lack of evidence.

Her defense lawyers say Knox felt pressured by police to name a suspect so her own interrogation could end.

Because of the time she served in prison before the acquittal, Knox didn’t have to serve the three-year sentence for the slander conviction. The court on Tuesday ordered her to pay 4,000 euros ($5,500) to the man, as well as the cost of the lost appeal.

Whether Knox ever returns to Italy to serve more prison time depends on a string of ifs and unknowns.

“Questions of extradition are not in the legal landscape at this point,” another Knox attorney, Theodore Simon, said on NBC TV.

If she is convicted by the Florence court, Knox could appeal that verdict to the Cassation Court. Should that appeal fail, Italy could seek her extradition from the United States.

Whether Italy actually requests extradition will be a political decision made by a future Italian government. It would then be up to U.S. officials to decide whether they will send Knox to Italy, and Dalla Vedova said U.S. authorities would carefully study all the case’s documentation to decide whether she had received fair trials.

U.S. and Italian authorities could also come to a deal that would keep Knox in the U.S.

For now, Knox has a memoir, “Waiting to Be Heard,” coming out April 30, for which publisher HarperCollins reportedly paid her $4 million. She still plans to appear in a prime-time special with Diane Sawyer to promote the book, according to ABC News.

In her statement, Knox took the Perugia prosecutors to task, saying they “must be made to answer” for the discrepancies in the case. She also said “my heart goes out to” Kercher’s family.

The Kercher family’s attorney, Francesco Maresca, called Tuesday’s ruling “what we wanted” and relayed a message from the late woman’s sister, Stephanie.

“To understand the truth about what happened that night is all we can do for her now,” the family’s message said.